The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression

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Abstract
Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet‐derived endothelial cell growth factor (PD‐ECGF). TP is overex‐pressed in various tumors and plays an important role in angiogenesis, tumor growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP. A novel, specific TP inhibitor, TPI, inhibits angiogenesis induced by overexpression of TP in KB/TP cells (human KB epidermoid carcinoma cells transfected with TP cDNA), as well as the growth and metastasis of KB/TP cells in vivo. 2‐Deoxy‐D‐ribose, the degradation product of thymidine generated by TP activity, has both angiogenic and chemotactic activity. Both 2‐deoxy‐D‐ribose and TP inhibit a hypoxia‐induced apoptotic pathway. These findings suggest that 2‐deoxy‐D‐ribose is a downstream mediator of TP function. 2‐Deoxy‐L‐ribose, a stereoisomer of 2‐deoxy‐D‐ribose, inhibits the promotion of angiogenesis, tumor growth and metastasis by TP. Although the mechanism of the action of 2‐deoxy‐D‐ribose is still unknown, 2‐deoxy‐L‐ribose may inhibit the physiological activities of 2‐deoxy‐D‐ribose, and consequently those of TP. Inhibition of TP activity and function appears to be a promising approach for the chemotherapy of various tumors.